The integrins are a large family of transmembrane glycoproteins that mediate cell-cell and cell-matrix interactions (1–5). All known members of this superfamily are non-covalently associated heterodimers composed of an α- and β-subunit. At present, 8 β-subunits (β1–β8) (6) and 16 α-subunits (α1–α9, αv, αM, αL, αX, αIIb, αE and αD) have been characterized (6–21), and these subunits associate to generate more than 20 different integrins. The β1-subunit has been shown to associate with ten different α-subunits, α1–α9 and αv, and to mediate interactions with extracellular matrix proteins such as collagens, laminins and fibronectin. The major collagen binding integrins are α1β1 and α2β1 (22–25). The integrins α3β1 and α9β1 have also been reported to interact with collagen (26, 27) although this interaction is not well understood (28). The extracellular N-terminal regions of the α and β integrin subunits are important in the binding of ligands (29, 30). The N-terminal region of the α-subunits is composed of a seven-fold repeated sequence (12, 31) containing FG and GAP consensus sequences. The repeats are predicted to fold into a β-propeller domain (32) with the last three or four repeats containing putative divalent cation binding sites. The α-integrin subunits α1, α2, αD, αE, αL, αM and αX contain a ˜200 amino acid inserted domain, the I-domain (A-domain), which shows similarity to sequences in von Willebrand factor, cartilage matrix protein and complement factors C2 and B (33, 34). The I-domain is localized between the second and third FG-GAP repeats, it contains a metal ion-dependent adhesion site (MIDAS) and it is involved in binding of ligands (35–38).
Chondrocytes, the only type of cells in cartilage, express a number of different integrins including α1β1, α2 β1, α3 β1, α5 β1, α6 β1, αvβ3, and αvβ5 (39–41). It has been shown that α1β1 and α2β1 mediate chondrocyte interactions with collagen type II (25) which is one of the major components in cartilage. It has also been shown that α2β1 is a receptor for the cartilage matrix protein chondroadherin (42).